The present invention relates to apparatuses, systems and methods of treating a patient. Particularly, the present invention relates to treating a body lumen. More particularly, the present invention relates to treating a blood vessel, such as in the treatment of heart disease.
Heart disease continues to be a leading cause of death in the United States. The mechanism of this disease is often progressive narrowing of coronary arteries by atherosclerotic plaque which can lead to acute myocardial infarction and disabling angina. Techniques to treat coronary atherosclerosis include percutaneous transluminal coronary angioplasty, (or PTCA, commonly referred to as balloon angioplasty), atherectomy, and coronary stenting. In each of these techniques, a guidewire is threaded to the site of coronary blockage and a treatment catheter is advanced over the guidewire. In balloon angioplasty, the guidewire is passed through the blockage and a balloon catheter is positioned within the blockage. The balloon is then inflated, compressing the atherosclerotic plaque against the walls of the coronary artery. In atherectomy, the treatment catheter is equipped with a cutting device which cuts the plaque away as the catheter is advanced through the blockage. In stenting, a stent, such as a metal or wire cage-like structure, is expanded and deployed against the plaque. Such stenting may be performed after balloon angioplasty or simultaneously with balloon angioplasty wherein the stent is mounted on the balloon. In each of these treatments, compression of the plaque and expansion of the coronary artery, or removal of the atherosclerotic plaque, often restores lumen patency.
Despite the overall initial success of these procedures, many patients undergoing these therapeutic procedures to clear blocked coronary arteries will suffer restenosis (re-blockage) at some point after the initial procedure. Such restenosis may be a manifestation of the general wound healing response. The injury induced by coronary intervention may cause platelet aggregation, inflammatory cell infiltration and release of growth factors, followed by smooth muscle cell proliferation and matrix formation. Thus, intimal hyperplasia due to vascular injury may be involved in the etiology of restenosis.
In an effort to inhibit such restenosis, numerous pharmacological agents and genes have been delivered to such arteries. Although agents and genes have been shown to inhibit restenosis in animal models, many have failed in human trials. One explanation for their failure is that suboptimal doses of agents were used in order to prevent side effects which occur from systemic administration of the higher doses. Consequently, the concept of localized intravascular delivery of therapeutics has become an attractive solution to overcome this limitation.
However, therapeutic agents coating conventional stents may have difficulty controllably passing into the vessel wall. As mentioned, stents mechanically prevent elastic recoil of the compressed plaque. A typical conventional stent is shown in FIGS. 1-2. FIG. 1 shows the coronary stent before expansion and FIG. 2 shows the stent after deployment. The stent consists of a metal lattice I with interstices 2. In use, a conventional balloon angioplasty procedure is often first performed to create a larger lumen in an occluded vessel, illustrated in FIG. 3A showing plaque 3 inside a coronary artery 4. Then, using a second balloon, the stent can be expanded at the site of the occlusion to a diameter slightly larger than the normal inner diameter of the vessel. The metal lattice 1 holds the compressed plaque against the vessel wall, as shown in FIG. 3B. If therapeutic agents are present coating the stent 1, the agents can pass into the vessel wall 4 on the right side, where there is little or no plaque, but agent penetration may be inhibited by the plaque 3 built up on the left side of the artery. The thickness of residual plaque in patients with coronary artery disease following angioplasty and stent placement may be in the range from 100 to 200 μm thick. In order to prevent restenosis, genes or drugs placed on the surface of a stent may benefit from a mechanism to penetrate the layer of compressed plaque barrier to gain entry to the vessel wall, particularly through the internal elastic lamina into the media and/or adventitia where the biology of restenosis resides.
In an effort to overcome the above described shortcomings, methods and apparatuses for drug and gene delivery are provided by Reed et al. (U.S. Pat. No. 6,197,013), incorporated by reference herein for all purposes. The Reed et al. devices allow diffuse delivery of a drug or gene to the coronary artery. This is accomplished by arrays of micromechanical probes present on the surface of the devices which penetrate the plaque and allow for efficient transport of therapeutic agents into the artery wall, in some cases directly to the artery media. The direct injection of therapeutic agents through the atherosclerotic plaque into the artery wall enables a wider variety of pharmaceuticals to be used when compared to the drugs used in current drug eluting stents. The probes can be part of a coronary stent which remains in the artery, or can be part of the angioplasty balloon, which is removed after the interventional procedure. The Reed et al devices differ from conventional methods in that a direct physical penetration of vascular plaque is accomplished.
While the Reed et al. devices represents a significant advancement, still further improvements would be desirable. The drug delivering probes of the Reed et al. devices preferably extend between 25 microns and 1000 microns from a surface of a deployment mechanism, such as a vascular stent, angioplasty balloon or an electrophoretic device. In most embodiments, particularly those including vascular stents, the probes extend this distance from the surface in the undeployed position. Deployment of the deployment mechanism involves radial force that pushes the probes such that they penetrate the vessel wall. The deployment mechanism preferably includes a removable housing, such as a sheath, in which the probes are disposed when the housing is in a closed state but is separate from the probes when the probes are deployed. This housing structure and the enclosed probes increase the minimum size of the deployment mechanism and possibly the risk of trauma to the vessel wall. Further, the designs of the Reed et al. devices suggest silicon micromachining techniques to produce the probes rather than conventional laser machining. It would be desirable to provide systems and devices having a lower profile for introduction to the blood vessel or body lumen. This would reduce the overall size of the device and possibly reduce the risk of trauma upon introduction to the vessel. Further it would be desirable to provide devices which may be produced by conventional laser machining.
In addition, it would be desirable to provide systems and devices which would secure the device in place and provide a mechanical seal to the vessel wall. One drawback of many conventional stents is the tendency of such stents to migrate downstream from the initial placement area. For example, due to irregularity in the vessel diameter or underexpansion of the stent, such stents have been observed to migrate downstream from the initial placement area. Thus, not only is the objective of the stent implantation not achieved, but the migrating stent may cause injury elsewhere in the vascular system. Further, a problem associated with grafts used for endovascular repair, particularly of aneurysms, is postprocedural leakage around the graft. Often, when leakage occurs, blood fills the aneurysmal sac due to gaps forming between the graft and the inner wall of the vessel. When vascular grafts fail due to leakage, the patient's condition is often compromised. Thus, it would be advantageous to provide systems and devices which reduce the risk of leakage. At least some of these objectives will be achieved by the inventions described hereinafter.